Thailand's national strategic plan on antimicrobial resistance: progress and challenges.

Antimicrobial resistance is a serious threat that affects all countries. The Global Action Plan on antimicrobial resistance and the United Nations Political Declaration on antimicrobial resistance set standards for countries to resolve antimicrobial resistance challenges under the One Health approach. We assess progress and challenges in implementing Thailand's national strategic plan on antimicrobial resistance 2017-2022, discuss interim outcomes and share lessons learnt. Major progress includes: establishing a national governance mechanism that leads high-impact policy on antimicrobial resistance and consolidates actions and multisectoral collaboration; creating a monitoring system and platform to track implementation of the strategic plan; and converting strategies of the strategic plan into actions such as controlling the distribution and use of antimicrobials in humans and animals. Interim results indicate that antimicrobial consumption in animals has nearly halved (exceeding the national goal of a 30% reduction) whereas other goals have not yet reached their targets. We have learnt that elevating antimicrobial resistance to high-level visibility and establishing a national governance mechanism is an important first step, and a monitoring and evaluation system should be developed in parallel with implementation. Securing funds is crucial. Policy coherence is needed to avoid duplication of actions. Highly ambitious goals, although yet to be achieved, can advance actions beyond expectations. Political commitment and collaboration across different sectors will continue to play important roles but might not be sustained without a well-designed governance structure to support long-term actions to address antimicrobial resistance.

La résistance aux antimicrobiens fait peser une sérieuse menace sur la planète tout entière. Le Plan d'action mondial pour combattre la résistance aux antimicrobiens ainsi que la Déclaration politique des Nations Unies sur la résistance aux agents antimicrobiens ont défini des normes pour les pays, afin qu'ils puissent faire face aux enjeux liés à la résistance aux antimicrobiens selon l'approche «One Health¼. Nous avons évalué les progrès et défis de la mise en œuvre du plan stratégique national de la Thaïlande en la matière pour 2017­2022, mais aussi discuté des résultats provisoires et partagé les enseignements tirés. Parmi les principaux progrès accomplis figurent l'établissement d'un mécanisme de gouvernance national pour mener une politique à impact élevé sur la résistance aux antimicrobiens, renforcer les actions et favoriser la collaboration intersectorielle; la création d'un système de surveillance et d'une plateforme pour suivre la mise en œuvre du plan stratégique; et enfin, la conversion des stratégies du plan en actions telles que le contrôle de la distribution et de l'usage des antimicrobiens chez les humains et les animaux. Les résultats provisoires indiquent que la consommation d'antimicrobiens chez les animaux a diminué de moitié (ce qui est supérieur à l'objectif national d'une réduction de 30%), tandis que les autres objectifs n'ont pas encore été atteints. Nous avons constaté qu'accroître la visibilité de la résistance aux antimicrobiens et instaurer un mécanisme de gouvernance national constituaient des étapes cruciales, et qu'un système de surveillance et d'évaluation devait être développé parallèlement à la mise en œuvre. L'obtention de financements est elle aussi essentielle. Une politique cohérente est nécessaire pour éviter de multiplier les actions similaires. Fixer des objectifs très ambitieux, même s'ils ne sont pas encore atteints, permet en outre de faire progresser les actions au-delà des attentes. Enfin, l'engagement politique et la collaboration entre différents secteurs continueront à jouer un rôle prépondérant, mais ne pourront peut-être pas se poursuivre sans une structure de gouvernance bien conçue, capable de soutenir des actions à long terme visant à remédier à la résistance aux antimicrobiens.

La resistencia a los antimicrobianos es una grave amenaza que afecta a todos los países. El Plan de Acción Mundial sobre la resistencia a los antimicrobianos y la Declaración Política de las Naciones Unidas sobre la resistencia a los antimicrobianos establecen normas para que los países resuelvan los problemas de resistencia a los antimicrobianos en el marco del enfoque «Una única salud¼. Evaluamos los avances y los desafíos en la aplicación del plan estratégico nacional de Tailandia sobre la resistencia a los antimicrobianos 2017-2022, analizamos los resultados provisionales y compartimos las lecciones aprendidas. Entre los principales avances se encuentran: el establecimiento de un mecanismo de gobernanza nacional que lidera la política de alto impacto sobre la resistencia a los antimicrobianos y consolida las acciones y la colaboración multisectorial; la creación de un sistema de seguimiento y una plataforma para seguir la aplicación del plan estratégico; y la conversión de las estrategias del plan estratégico en acciones como el control de la distribución y el uso de antimicrobianos en humanos y animales. Los resultados provisionales indican que el consumo de antimicrobianos en animales se ha reducido casi a la mitad (superando el objetivo nacional de una reducción del 30 %), mientras que otros objetivos aún no han alcanzado sus metas. Hemos aprendido que elevar la resistencia a los antimicrobianos a una visibilidad de alto nivel y establecer un mecanismo de gobernanza nacional es un primer paso importante, y que debe desarrollarse un sistema de seguimiento y evaluación en paralelo a la implementación. Asegurar los fondos es crucial. La coherencia política es necesaria para evitar la duplicación de acciones. Unos objetivos muy ambiciosos, aunque todavía no se hayan alcanzado, pueden hacer avanzar las acciones más allá de las expectativas. El compromiso político y la colaboración entre los distintos sectores seguirán desempeñando un papel importante, pero podrían no mantenerse sin una estructura de gobernanza bien diseñada que apoye las acciones a largo plazo para hacer frente a la resistencia a los antimicrobianos.

Etiology and Clinical Characteristics of Severe Pneumonia Among Young Children in Thailand: Pneumonia Etiology Research for Child Health (PERCH) Case-Control Study Findings, 2012-2013.

BACKGROUND: Pneumonia remains the leading cause of death among children <5 years of age beyond the neonatal period in Thailand. Using data from the Pneumonia Etiology Research for Child Health (PERCH) Study, we provide a detailed description of pneumonia cases and etiology in Thailand to inform local treatment and prevention strategies in this age group. METHODS: PERCH, a multi-country case-control study, evaluated the etiology of hospitalized cases of severe and very severe pneumonia among children 1-59 months of age. The Thailand site enrolled children for 24 consecutive months during January 2012-February 2014 with staggered start dates in 2 provinces. Cases were children hospitalized with pre-2013 WHO-defined severe or very severe pneumonia. Community controls were randomly selected from health services registries in each province. Analyses were restricted to HIV-negative cases and controls. We calculated adjusted odds ratios (ORs) and 95% CIs comparing organism prevalence detected by nasopharyngeal/oropharyngeal (NP/OP) polymerase chain reaction between cases and controls. The PERCH Integrated Analysis (PIA) used Bayesian latent variable analysis to estimate pathogen-specific etiologic fractions and 95% credible intervals. RESULTS: Over 96% of both cases (n = 223) and controls (n = 659) had at least 1 organism detected; multiple organisms were detected in 86% of cases and 88% of controls. Among 98 chest Radiograph positive (CXR+) cases, respiratory syncytial virus (RSV) had the highest NP/OP prevalence (22.9%) and the strongest association with case status (OR 20.5; 95% CI: 10.2, 41.3) and accounted for 34.6% of the total etiologic fraction. Tuberculosis (TB) accounted for 10% (95% CrI: 1.6-26%) of the etiologic fraction among CXR+ cases. DISCUSSION: More than one-third of hospitalized cases of severe and very severe CXR+ pneumonia among children 1-59 months of age in Thailand were attributable to RSV. TB accounted for 10% of cases, supporting evaluation for TB among children hospitalized with pneumonia in high-burden settings. Similarities in pneumonia etiology in Thailand and other PERCH sites suggest that global control strategies based on PERCH study findings are relevant to Thailand and similar settings.

Molecular epidemiology of carbapenem-resistant Enterobacterales in Thailand, 2016-2018.

BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) is a global threat. Enterobacterales develops carbapenem resistance through several mechanisms, including the production of carbapenemases. We aim to describe the prevalence of Carbapenem-resistant Enterobacterales (CRE) with and without carbapenemase production and distribution of carbapenemase-producing (CP) genes in Thailand using 2016-2018 data from a national antimicrobial resistance surveillance system developed by the Thailand National Institute of Health (NIH). METHODS: CRE was defined as any Enterobacterales resistant to ertapenem, imipenem, or meropenem. Starting in 2016, 25 tertiary care hospitals from the five regions of Thailand submitted the first CRE isolate from each specimen type and patient admission to Thailand NIH, accompanied by a case report form with patient information. NIH performed confirmatory identification and antimicrobial susceptibility testing and performed multiplex polymerase chain reaction testing to detect CP-genes. Using 2016-2018 data, we calculated proportions of CP-CRE, stratified by specimen type, organism, and CP-gene using SAS 9.4. RESULTS: Overall, 4,296 presumed CRE isolates were submitted to Thailand NIH; 3,946 (93%) were confirmed CRE. Urine (n = 1622, 41%) and sputum (n = 1380, 35%) were the most common specimen types, while blood only accounted for 323 (8%) CRE isolates. The most common organism was Klebsiella pneumoniae (n = 2660, 72%), followed by Escherichia coli (n = 799, 22%). The proportion of CP-CRE was high for all organism types (range: 85-98%). Of all CRE isolates, 2909 (80%) had one CP-gene and 629 (17%) had > 1 CP-gene. New Delhi metallo-beta-lactamase (NDM) was the most common CP-gene, present in 2392 (65%) CRE isolates. K. pneumoniae carbapenemase (KPC) and Verona integron-encoded metallo-ß-lactamase (VIM) genes were not detected among any isolates. CONCLUSION: CP genes were found in a high proportion (97%) of CRE isolates from hospitals across Thailand. The prevalence of NDM and OXA-48-like genes in Thailand is consistent with pattern seen in Southeast Asia, but different from that in the United States and other regions. As carbapenemase testing is not routinely performed in Thailand, hospital staff should consider treating all patients with CRE with enhanced infection control measures; in line with CDC recommendation for enhanced infection control measures for CP-CRE because of their high propensity to spread.

Upper Respiratory Tract Co-detection of Human Endemic Coronaviruses and High-density Pneumococcus Associated With Increased Severity Among HIV-Uninfected Children Under 5 Years Old in the PERCH Study.

BACKGROUND: Severity of viral respiratory illnesses can be increased with bacterial coinfection and can vary by sex, but influence of coinfection and sex on human endemic coronavirus (CoV) species, which generally cause mild to moderate respiratory illness, is unknown. We evaluated CoV and pneumococcal co-detection by sex in childhood pneumonia. METHODS: In the 2011-2014 Pneumonia Etiology Research for Child Health study, nasopharyngeal and oropharyngeal (NP/OP) swabs and other samples were collected from 3981 children <5 years hospitalized with severe or very severe pneumonia in 7 countries. Severity by NP/OP detection status of CoV (NL63, 229E, OC43 or HKU1) and high-density (≥6.9 log10 copies/mL) pneumococcus (HDSpn) by real-time polymerase chain reaction was assessed by sex using logistic regression adjusted for age and site. RESULTS: There were 43 (1.1%) CoV+/HDSpn+, 247 CoV+/HDSpn-, 449 CoV-/HDSpn+ and 3149 CoV-/HDSpn- cases with no significant difference in co-detection frequency by sex (range 51.2%-64.0% male, P = 0.06). More CoV+/HDSpn+ pneumonia was very severe compared with other groups for both males (13/22, 59.1% versus range 29.1%-34.7%, P = 0.04) and females (10/21, 47.6% versus 32.5%-43.5%, P = 0.009), but only male CoV+/HDSpn+ required supplemental oxygen more frequently (45.0% versus 20.6%-28.6%, P < 0.001) and had higher mortality (35.0% versus 5.3%-7.1%, P = 0.004) than other groups. For females with CoV+/HDSpn+, supplemental oxygen was 25.0% versus 24.8%-33.3% (P = 0.58) and mortality was 10.0% versus 9.2%-12.9% (P = 0.69). CONCLUSIONS: Co-detection of endemic CoV and HDSpn was rare in children hospitalized with pneumonia, but associated with higher severity and mortality in males. Findings may warrant investigation of differences in severity by sex with co-detection of HDSpn and SARS-CoV-2.

Draft Genome Sequence of Invasive Salmonella enterica Serovar Cannstatt Harboring mcr-1.1, Isolated from a Fatal Sepsis Case.

Here, we report the whole-genome sequence of multidrug-resistant Salmonella enterica serovar Cannstatt harboring mcr-1.1, isolated from a fatal sepsis case. Genomic analysis revealed that the isolate was sequence type 2390 carrying mcr-1.1, bla CTX-M-14, aac(3)IId, aac(6')Iaa, floR, qnrS1, sul2, tetA, and tetM Three Inc plasmids were observed, including the IncX4 plasmid containing mcr-1.1.

Pneumococcal colonization prevalence and density among Thai children with severe pneumonia and community controls.

BACKGROUND: Pneumococcal colonization prevalence and colonization density, which has been associated with invasive disease, can offer insight into local pneumococcal ecology and help inform vaccine policy discussions. METHODS: The Pneumonia Etiology Research for Child Health Project (PERCH), a multi-country case-control study, evaluated the etiology of hospitalized cases of severe and very severe pneumonia among children aged 1-59 months. The PERCH Thailand site enrolled children during January 2012-February 2014. We determined pneumococcal colonization prevalence and density, and serotype distribution of colonizing isolates. RESULTS: We enrolled 224 severe/very severe pneumonia cases and 659 community controls in Thailand. Compared to controls, cases had lower colonization prevalence (54.5% vs. 62.5%, p = 0.12) and lower median colonization density (42.1 vs. 210.2 x 103 copies/mL, p <0.0001); 42% of cases had documented antibiotic pretreatment vs. 0.8% of controls. In no sub-group of assessed cases did pneumococcal colonization density exceed the median for controls, including cases with no prior antibiotics (63.9x103 copies/mL), with consolidation on chest x-ray (76.5x103 copies/mL) or with pneumococcus detected in whole blood by PCR (9.3x103 copies/mL). Serotype distribution was similar among cases and controls, and a high percentage of colonizing isolates from cases and controls were serotypes included in PCV10 (70.0% and 61.8%, respectively) and PCV13 (76.7% and 67.9%, respectively). CONCLUSIONS: Pneumococcal colonization is common among children aged <5 years in Thailand. However, colonization density was not higher among children with severe pneumonia compared to controls. These results can inform discussions about PCV introduction and provide baseline data to monitor PCV impact after introduction in Thailand.

Streptococcus agalactiae infections and clinical relevance in adults, Thailand.

Streptococcus agalactiae is an important pathogen that causes infections in neonates and adults; infections especially in nonpregnant adults are increasing worldwide. Of 1736 S. agalactiae isolates from individuals throughout Thailand, serotypes III (46.4%) and V (21%) were demonstrated to be the most common serotypes. Human cases (56.5% female and 43.5% male) could be found all year round, with the peak occurring more frequently during the rainy season (May-October). The mortality rate of S. agalactiae infections was 11.6%, and serotype III was the most common serotype involved. Serotype III was strongly significantly (P value <0.001) correlated with meningitis (odds ratio [OR] = 26.72), sepsis (OR = 5.56), and septic arthritis (OR = 22.79). Serotype V was more associated with urinary tract infection than other serotypes. (P value = 0.005; OR = 2.32).

Whole-Genome Sequencing of Clinically Isolated Carbapenem-Resistant Enterobacterales Harboring mcr Genes in Thailand, 2016-2019.

Mobile colistin-resistant genes (mcr) have become an increasing public health concern. Since the first report of mcr-1 in Thailand in 2016, perspective surveillance was conducted to explore the genomic characteristics of clinical carbapenem-resistant Enterobacterales (CRE) isolates harboring mcr in 2016-2019. Thirteen (0.28%) out of 4,516 CRE isolates were found to carry mcr genes, including 69.2% (9/13) of E. coli and 30.8% (4/13) of K. pneumoniae isolates. Individual mcr-1.1 was detected in eight E. coli (61.5%) isolates, whereas the co-occurrence of mcr-1.1 and mcr-3.5 was seen in only one E. coli isolate (7.7%). No CRE were detected carrying mcr-2, mcr-4, or mcr-5 through to mcr-9. Analysis of plasmid replicon types carrying mcr revealed that IncX4 was the most common (61.5%; 8/13), followed by IncI2 (15.4%; 2/13). The minimum inhibitory concentration values for colistin were in the range of 4-16 µg/ml for all CRE isolates harboring mcr, suggesting they have 100% colistin resistance. Clermont phylotyping of nine mcr-harboring carbapenem-resistant E. coli isolates demonstrated phylogroup C was predominant in ST410. In contrast, ST336 belonged to CC17, and the KL type 25 was predominant in carbapenem-resistant K. pneumoniae isolates. This report provides a comprehensive insight into the prevalence of mcr-carrying CRE from patients in Thailand. The information highlights the importance of strengthening official active surveillance efforts to detect, control, and prevent mcr-harboring CRE and the need for rational drug use in all sectors.

Molecular epidemiology and antimicrobial susceptibility of outbreak-associated Corynebacterium diphtheriae in Thailand, 2012.

Infections caused by Corynebacterium diphtheriae remain endemic in many countries. Since the implementation of the DTP (Diphtheria-Tetanus-Pertussis) vaccination program in 1977, only sporadic diphtheria cases have been reported in Thailand. In 2012, a diphtheria outbreak occurred in rural Thailand and 38 cases were reported, with the majority being adults (mean 22.1 years, range 5-72 years). The current study determined the genetic diversity of C. diphtheriae isolated from 83 individuals associated with either sporadic (n = 34) from 1994, 1996, 1997, 1998, 1999, 2000, 2012, and 2018, or 2012 outbreak (n = 49) diphtheria occurrences in Thailand. Antimicrobial susceptibility testing was performed on 41/83 isolates using broth microdilution. All sporadic (n = 27) and epidemic (n = 14) C. diphtheriae isolates (41/41; 100%) were susceptible to erythromycin (≤0.5 µg/ml), clindamycin (≤0.5 µg/ml), gentamicin (≤ 4 µg/ml), ciprofloxacin (≤1 µg/ml), and vancomycin (2 µg/ml), except tetracycline with a resistance rate of 34.1% (14/41 isolates). All isolates were intermediately resistant to penicillin (MIC range, 0.25-2 µg/ml). Multilocus sequence typing (MLST) revealed 17 sequence types (STs) among 83C. diphtheriae isolates. For the 2012 outbreak isolates, the predominant ST was ST243 (n = 34/49; 69.4%), followed by ST245 (n = 5/49; 10.2%) and ST244 (n = 4/49; 8.1%), whereas the main STs among the sporadic isolates were ST248 (n = 15/34; 44.1%), followed by ST209 (n = 7/34; 20.6%) and ST258 (n = 3/34; 8.8%). The ST243 outbreak strain was a single-locus variant of sporadic ST258. Phylogenetic analysis using concatenated sequences of 7 MLST genes from 17 STs revealed that ST243, ST248, and ST258 were located in the same cluster and ST243 appeared to have evolved from ST258, an endemic strain. This study highlights the importance of epidemiological surveillance together with characterization of C. diphtheriae strains to help inform the future control and prevention of diphtheria.

Pneumococcal pneumonia prevalence among adults with severe acute respiratory illness in Thailand - comparison of Bayesian latent class modeling and conventional analysis.

BACKGROUND: Determining the etiology of pneumonia is essential to guide public health interventions. Diagnostic test results, including from polymerase chain reaction (PCR) assays of upper respiratory tract specimens, have been used to estimate prevalence of pneumococcal pneumonia. However limitations in test sensitivity and specificity and the specimen types available make establishing a definitive diagnosis challenging. Prevalence estimates for pneumococcal pneumonia could be biased in the absence of a true gold standard reference test for detecting Streptococcus pneumoniae. METHODS: We conducted a case control study to identify etiologies of community acquired pneumonia (CAP) from April 2014 through August 2015 in Thailand. We estimated the prevalence of pneumococcal pneumonia among adults hospitalized for CAP using Bayesian latent class models (BLCMs) incorporating results of real-time polymerase chain reaction (qPCR) testing of upper respiratory tract specimens and a urine antigen test (UAT) from cases and controls. We compared the prevalence estimate to conventional analyses using only UAT as a reference test. RESULTS: The estimated prevalence of pneumococcal pneumonia was 8% (95% CI: 5-11%) by conventional analyses. By BLCM, we estimated the prevalence to be 10% (95% CrI: 7-16%) using binary qPCR and UAT results, and 11% (95% CrI: 7-17%) using binary UAT results and qPCR cycle threshold (Ct) values. CONCLUSIONS: BLCM suggests a > 25% higher prevalence of pneumococcal pneumonia than estimated by a conventional approach assuming UAT as a gold standard reference test. Higher quantities of pneumococcal DNA in the upper respiratory tract were associated with pneumococcal pneumonia in adults but the addition of a second specific pneumococcal test was required to accurately estimate disease status and prevalence. By incorporating the inherent uncertainty of diagnostic tests, BLCM can obtain more reliable estimates of disease status and improve understanding of underlying etiology.

Pertussis surveillance in a children hospital in Bangkok, Thailand.

OBJECTIVES: To investigate the incidence, clinical characteristics and cost associated with pertussis in Thai children with persistent cough. METHODS: A prospective study was conducted among children aged 0-18 years with persistent cough for ≥7days with at least one of the following: paroxysm, inspiratory whooping, or post-tussive emesis. Nasopharyngeal swabs were obtained and tested for pertussis real time polymerase chain reaction (RT-PCR). RESULTS: 19.6% of children (28 out of 143) had pertussis confirmed by RT-PCR, 75% of cases occurred in children who were too young to complete their primary series of vaccine. Paroxysm and post-tussive emesis were the most consistent clinical features, identified in 96% and 93% of cases, respectively, whooping was found in only 18%. Pertussis cases were more likely to have household cough contact (64% versus 30%, p<0.001), be hospitalized (79% versus 58%, p=0.048) and experience protracted duration of cough (47 vs. 20 days, p<0.001) compare to their counterpart. CONCLUSION: Pertussis in Thai children is not infrequent and the common age group is young infant before completion of primary series of pertussis vaccine at six months of age, underline the importance of maternal pertussis immunization.

Population-based bloodstream infection surveillance in rural Thailand, 2007-2014.

BACKGROUND: Bloodstream infection (BSI) surveillance is essential to characterize the public health threat of bacteremia. We summarize BSI epidemiology in rural Thailand over an eight year period. METHODS: Population-based surveillance captured clinically indicated blood cultures and associated antimicrobial susceptibility results performed in all 20 hospitals in Nakhon Phanom (NP) and Sa Kaeo (SK) provinces. BSIs were classified as community-onset (CO) when positive cultures were obtained ≤2 days after hospital admission and hospital-onset (HO) thereafter. Hospitalization denominator data were available for incidence estimates for 2009-2014. RESULTS: From 2007 to 2014 a total of 11,166 BSIs were identified from 134,441 blood cultures. Annual CO BSI incidence ranged between 89.2 and 123.5 cases per 100,000 persons in SK and NP until 2011. Afterwards, CO incidence remained stable in SK and increased in NP, reaching 155.7 in 2013. Increases in CO BSI incidence over time were limited to persons aged ≥50 years. Ten pathogens, in rank order, accounted for > 65% of CO BSIs in both provinces, all age-groups, and all years: Escherichia coli, Klebsiella pneumoniae, Burkholderia pseudomallei, Staphylococcus aureus, Salmonella non-typhi spp., Streptococcus pneumoniae, Acinetobacter spp., Streptococcus agalactiae, Streptococcus pyogenes, Pseudomonas aeruginosa. HO BSI incidence increased in NP from 0.58 cases per 1000 hospitalizations in 2009 to 0.91 in 2014, but were higher (ranging from 1.9 to 2.3) in SK throughout the study period. Extended-spectrum beta-lactamase production among E. coli isolates and multi-drug resistance among Acinetobacter spp. isolates was common (> 25% of isolates), especially among HO cases (> 50% of isolates), and became more common over time, while methicillin-resistance among S. aureus isolates (10%) showed no clear trend. Carbapenem-resistant Enterobacteriaceae were documented in 2011-2014. CONCLUSIONS: Population-based surveillance documented CO BSI incidence estimates higher than previously reported from Thailand and the region, with temporal increases seen in older populations. The most commonly observed pathogens including resistance profiles were similar to leading pathogens and resistance profiles worldwide, thus; prevention strategies with demonstrated success elsewhere may prove effective in Thailand.

Enhanced surveillance for severe pneumonia, Thailand 2010-2015.

BACKGROUND: The etiology of severe pneumonia is frequently not identified by routine disease surveillance in Thailand. Since 2010, the Thailand Ministry of Public Health (MOPH) and US CDC have conducted surveillance to detect known and new etiologies of severe pneumonia. METHODS: Surveillance for severe community-acquired pneumonia was initiated in December 2010 among 30 hospitals in 17 provinces covering all regions of Thailand. Interlinked clinical, laboratory, pathological and epidemiological components of the network were created with specialized guidelines for each to aid case investigation and notification. Severe pneumonia was defined as chest-radiograph confirmed pneumonia of unknown etiology in a patient hospitalized ≤48 h and requiring intubation with ventilator support or who died within 48 h after hospitalization; patients with underlying chronic pulmonary or neurological disease were excluded. Respiratory and pathological specimens were tested by reverse transcription polymerase chain reaction for nine viruses, including Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and 14 bacteria. Cases were reported via a secure web-based system. RESULTS: Of specimens from 972 cases available for testing during December 2010 through December 2015, 589 (60.6%) had a potential etiology identified; 399 (67.8%) were from children aged < 5 years. At least one viral agent was detected in 394 (40.5%) cases, with the most common of single vial pathogen detected being respiratory syncytial virus (RSV) (110/589, 18.7%) especially in children under 5 years. Bacterial pathogens were detected in 341 cases of which 67 cases had apparent mixed infections. The system added MERS-CoV testing in September 2012 as part of Thailand's outbreak preparedness; no cases were identified from the 767 samples tested. CONCLUSIONS: Enhanced surveillance improved the understanding of the etiology of severe pneumonia cases and improved the MOPH's preparedness and response capacity for emerging respiratory pathogens in Thailand thereby enhanced global health security. Guidelines for investigation of severe pneumonia from this project were incorporated into surveillance and research activities within Thailand and shared for adaption by other countries.

Density of Upper Respiratory Colonization With Streptococcus pneumoniae and Its Role in the Diagnosis of Pneumococcal Pneumonia Among Children Aged <5 Years in the PERCH Study.

BACKGROUND.: Previous studies suggested an association between upper airway pneumococcal colonization density and pneumococcal pneumonia, but data in children are limited. Using data from the Pneumonia Etiology Research for Child Health (PERCH) study, we assessed this potential association. METHODS.: PERCH is a case-control study in 7 countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. Cases were children aged 1-59 months hospitalized with World Health Organization-defined severe or very severe pneumonia. Controls were randomly selected from the community. Microbiologically confirmed pneumococcal pneumonia (MCPP) was confirmed by detection of pneumococcus in a relevant normally sterile body fluid. Colonization density was calculated with quantitative polymerase chain reaction analysis of nasopharyngeal/oropharyngeal specimens. RESULTS.: Median colonization density among 56 cases with MCPP (MCPP cases; 17.28 × 106 copies/mL) exceeded that of cases without MCPP (non-MCPP cases; 0.75 × 106) and controls (0.60 × 106) (each P < .001). The optimal density for discriminating MCPP cases from controls using the Youden index was >6.9 log10 copies/mL; overall, the sensitivity was 64% and the specificity 92%, with variable performance by site. The threshold was lower (≥4.4 log10 copies/mL) when MCPP cases were distinguished from controls who received antibiotics before specimen collection. Among the 4035 non-MCPP cases, 500 (12%) had pneumococcal colonization density >6.9 log10 copies/mL; above this cutoff was associated with alveolar consolidation at chest radiography, very severe pneumonia, oxygen saturation <92%, C-reactive protein ≥40 mg/L, and lack of antibiotic pretreatment (all P< .001). CONCLUSIONS.: Pneumococcal colonization density >6.9 log10 copies/mL was strongly associated with MCPP and could be used to improve estimates of pneumococcal pneumonia prevalence in childhood pneumonia studies. Our findings do not support its use for individual diagnosis in a clinical setting.

Emergence of plasmid-mediated colistin resistance and New Delhi metallo-ß-lactamase genes in extensively drug-resistant Escherichia coli isolated from a patient in Thailand.

We reported a case of Escherichia coli with colistin resistance and an extensively drug-resistant phenotype. Molecular analysis revealed that the isolate carried mcr-1 and multiple ß-lactamase genes includingblaNDM1, blaCTX-M-15, blaTEM1, and blaCMY-2. This is the first report of a clinical mcr-1 isolate in Thailand highlighting the urgent need for a comprehensive antimicrobial resistance containment strategy to prevent further spread.

Clinical Specimen-Direct LAMP: A Useful Tool for the Surveillance of blaOXA-23-Positive Carbapenem-Resistant Acinetobacter baumannii.

Healthcare-associated infections are a leading cause of morbidity and mortality worldwide. Treatment is increasingly complicated by the escalating incidence of antimicrobial resistance. Among drug-resistant pathogens, carbapenem-resistant Acinetobacter baumannii (CRAb) is of increasing concern because of the limited applicable therapies and its expanding global distribution in developed countries and newly industrialized countries. Therefore, a rapid detection method that can be used even in resource-poor countries is urgently required to control this global public health threat. Conventional techniques, such as bacterial culture and polymerase chain reaction (PCR), are insufficient to combat this threat because they are time-consuming and laborious. In this study, we developed a loop-mediated isothermal amplification (LAMP) method for detecting blaOXA-23-positive CRAb, the most prevalent form of CRAb in Asia, especially in Thailand, and confirmed its efficacy as a surveillance tool in a clinical setting. Clinical samples of sputum and rectal swabs were collected from patients in a hospital in Bangkok and used for LAMP assays. After boiling and centrifugation, the supernatants were used directly in the assay. In parallel, a culture method was used for comparison purposes to evaluate the specificity and sensitivity of LAMP. As a first step, a total of 120 sputum samples were collected. The sensitivity of LAMP was 88.6% (39/44), and its specificity was 92.1% (70/76) using the culture method as the "gold standard". When surveillance samples including sputum and rectal swabs were analyzed with the LAMP assay, its sensitivity was 100.0%. This method enables the direct analysis of clinical specimens and provides results within 40 minutes of sample collection, making it a useful tool for surveillance even in resource-poor countries.

Thailand Antimicrobial Resistance Containment and Prevention Program.

The Thailand Antimicrobial Resistance (AMR) Containment and Prevention Program was founded to develop, co-ordinate and implement AMR Containment and Prevention (AMRCP) operational actions in Thailand following the 'One Health' approach. This article summarises the ten AMRCP operational actions initiated during the initial phase of the programme from 2012 to 2016: estimating the national AMR burden; establishing the dynamics of AMR chains to understand how AMR in Thailand develops and spreads; developing a national AMRCP infrastructure; developing laboratory and information technology systems for surveillance of AMR, antibiotic use and hospital-acquired infections; regulating the use and distribution of antibiotics in humans and food animals; generating local evidence for promoting responsible use of antibiotics and efficient practices for infection prevention and control; designing AMRCP campaigns; creating an AMRCP package; implementing the AMRCP package in selected pilot communities; and conducting research and development on diagnostics, therapy and prevention of antimicrobial-resistant bacterial infections. The programme's core campaign is to stop producing AMR by promoting responsible use of antibiotics, and to stop the acquisition and transmission of AMR by promoting good sanitation and hygiene as well as compliance with infection control and prevention practices.